Is SPARC an evolutionarily conserved collagen chaperone?

The construction of collagen fiber scaffolds, which provide the structural integrity of the extracellular matrix of connective tissues and basement membranes, is initiated by a complex mechanism of protein-folding, whereby pro-collagen alpha-chains are assembled into triple-helical procollagen molecules. This unique assembly of the procollagen molecules is guided by several endoplasmic reticulum resident molecular chaperones, including HSP47, which dissociates from procollagen molecules prior to their transport from the endoplasmic reticulum into the cis-Golgi network. SPARC, an evolutionarily conserved collagen-binding glycoprotein, which is frequently co-expressed with collagen in rapidly remodeling tissues, binds to the triple-helical region of procollagen molecules. Analysis of data from genome projects indicates that specific amino acids and sequences in SPARC that are critical for collagen binding are evolutionarily conserved in organisms ranging from nematodes to mammals. Studies of invertebrates, which do not encode HSP47, indicate that SPARC expression is required for the deposition of collagen IV in basal lamina during embryonic development. In mammals, defects in collagen deposition have been observed in normal and wound-healing tissues in the absence of SPARC expression. Based on these and other observations, we propose that intracellular SPARC acts as a collagen molecular chaperone in the endoplasmic reticulum, and that in higher organisms, SPARC acts in concert with HSP47 to ensure that only correctly folded procollagen molecules exit the endoplasmic reticulum. In contrast to HSP47, SPARC is transported from the endoplasmic reticulum through the Golgi network and into secretory vesicles for exocytosis at the plasma membrane. Hence, SPARC may also play a role in regulating post-endoplasmic reticulum events that promote collagen fibrillogenesis.